The qualitative or quantitative determination of analytes in test samples continues to be important in the diagnoses of physiological and non-physiological conditions. The analysis of a test sample mixed with reagents results in a detectable signal with and without the aid of instrumentation.
Methods and devices have been provided which give determinations of a variety of analytes in a test sample. Of particular interest for purposes of the present invention are small, disposable devices. Such devices generally involve either a strip or a track device.
Porous devices generally employ some form of porous material which carries a fluid through the device. These devices are generally in the form of sheets, strips, dipsticks, etc. Strip devices advantageously have a large surface area and small pores. One of the disadvantages of devices utilizing such materials is that the porous material can vary from lot to lot due to the random process in forming the devices. The variations can cause differences in the performance of the devices.
Track devices provide uniform surfaces which are readily reproducible yet provide too large a spacing to allow for diffusion of analyte and subsequent capture at an internal surface in a reasonable length of time.
Therefore, it would be advantageous to create small, disposable devices which have the dimensional reproducibility of track devices and the small pores and large surface area of devices employing porous material. The problems of porous devices and track devices would then be simultaneously solved.
Several processes have been used to create small devices in the electronic industry. For example, Munchmeyer et al., Rev. Sci. Instrum., 63 (1) 713-721, (1992), discloses LIGA technology for producing optical and electrical microcomponents utilizing synchotron radiation lithography to produce masters. Angell et al., Scientific American, 248:44-55 (1983) teaches etching by micromachining technology into silicon wafers for microelectronics purposes. Manz et al., Trends in Analytical Chemistry, Vol. 10, No. 5, pp. 144-149, (1991), discloses reproducible micromachined monocrystalline silicon and glass for flow injection analysis and detector cells which provide for faster chromatographic and electrophoretic separations.
The trend to small devices is not limited to the electronics industry. Sato et al., Sensors and Actuators, A21-A23, pp. 948-953, (1990), discloses micromechanical silicon devices which permits one-to-one cell fusion operations between two different cell groups to be carried out simultaneously. Cells were found to fuse successfully in the microchambers.
U.S. Pat. No. 4,789,628 to Nayak discloses a plurality of spaced projections extending upward from the well bottom to provide increased surface area for ligand:anti-ligand assays. The plurality of spaced projections forms an interconnecting channel. However, the large sizes of the projections and large widths of the channels do not provide for microvolume assays or rapid signal development with low level analytes.
WO 93/22053 A1 to Wilding et al., discloses microfabricated detection devices which detect analyte in a test sample. The device has a micrometer scale channel extending from the inlet port. The channels were constructed by micromachining into silicon. Binding moieties line the channel which provides for analyte detection.
The current analytical techniques, namely porous and track devices, do not provide materials which result in satisfactory assay performance. There is a need for a reproducible device which permits microvolumes of fluid flow at acceptable rates and capture of analyte with acceptable efficiencies.